Tuberculosis is a stubborn disease, born of yet more stubborn microbes. While many bacterial infections resolve within days of starting antibiotics, tuberculosis often refuses to budge for around six months and, in some cases, may never release its vice grip on the human body. It claimed 1.5 million lives in 2020, second only to COVID-19 among infectious diseases. 

Just because you are exposed to a pathogen does not mean you will become sick. Increasingly, scientists have shown that genetics play a central role in determining whether the pathogens that cause a wide range of disease—including influenza, warts, and COVID-19—end up causing serious diseases.

About one in five people are infected with Mycobacterium tuberculosis, the microbe that causes tuberculosis. Most, however, will never develop symptoms; and for decades researchers have been stumped as to why some people are more vulnerable to the bacterium than others. Now, Rockefeller scientist Jean-Laurent Casanova has identified a genetic condition that makes the immune system susceptible to mycobacterial attack.

If you live in the United States, you are unlikely to come into contact with the microbe that causes tuberculosis. Your odds of encountering the microbe are so low, in fact, that risk factors for the disease can easily go unnoticed: If you happened to carry a gene that predisposed you to tuberculosis, you likely wouldn’t know.

For decades, doctors have been using antibiotics to fight tuberculosis (TB). And consistently, the microbe responsible for the disease, Mycobacterium tuberculosis, has been fighting back. When confronted with current drugs, such as the antibiotic rifamycin, the bacterium often mutates in ways that make it resistant to the treatment.

Tuberculosis, which infects roughly one quarter of the world’s population and kills nearly two million people a year, is not only deadly but ancient: signs of the disease have been found in Egyptian mummies. Despite its age, Mycobacterium tuberculosis, the pathogen that causes the illness, continues to learn new tricks. It has a particular knack for evolving antibiotic resistance, leaving hundreds of thousands of people with few treatment options.

With the first detailed analysis of a cellular component from a close relative of the pathogen that causes tuberculosis, Rockefeller scientists are suggesting strategies for new drugs to curb this growing health problem. Each year, nearly half a million people around the world are infected with mutant TB strains capable of evading existing antibiotics.

A team of researchers led by scientists at Rockefeller University have discovered that a protein once thought to be mainly involved in antiviral immunity is in fact more important in fighting bacterial infections and could provide new mechanisms for treating diseases like tuberculosis, which is increasingly becoming resistant to antibiotic medication.